Real-time label-free technologies such as surface plasmon resonance biosensors provide high-resolution information about the kinetics, affinity, stoichiometry, activity, and specificity, of two (or more) binding partners. While the application f biosensors is well established, current instrumentation has limited sampling throughput. Screens of even a fairly small chemical library (e.g., 3000-5000 compounds) require days to weeks to complete using traditional label-free instruments. Because of the quality of the data generated by SPR, drug discovery scientists are clamoring to use enhanced biosensors as a screening tool for small molecule applications; however, lack of throughput hinders their ability to move in this direction. We propose to develop a biosensor platform that has increased throughput yet maintains the data quality and ease of use to which researchers are accustomed. We will couple our novel Continuous Flow Microspotter (CFM) with an enhanced-sensitivity SPR biosensor from BiOptix to enable label-free screening and kinetic analsyis of small molecules and biologics. In high-throughput screening mode our 96 channel integrated CFM/E-biosensor platform will be capable of collecting data for >30,000 samples in less than 24 hours - a sampling rate 24x faster than fastest small-molecule capable label-free biosensor, the Biacore 4000.